Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of lamellarin alkaloids using orthoester-masked ?-keto acids.

ABSTRACT: Pyruvic acid and other ?-keto acids are frequently encountered as intermediates in metabolic pathways, yet their application in total synthesis has met with limited success. In this work, we present a bioinspired strategy that utilizes highly functionalized OBO (oxabicyclo[2.2.2]octyl) orthoester masked ?-ketoacids as key intermediates for the construction of both type I and II lamellarin alkaloids. Lamellarin D was synthesized, via a key 1,4-dicarbonyl, in 7 steps and 22% yield from pyruvic acid. Key steps in the synthesis involve one-pot double enolate functionalisation of 1 followed by double annulation to form the target pyrrole/N-vinyl pyrrole core and late-stage direct C-H arylation. Lastly, a novel OBO-masked ?-cyano ketone, synthesized from 1, proved to be a valuable intermediate for construction of the type II lamellarin core via HBr-mediated cyclisation. In this way, lamellarin Q was synthesized in 7 steps and 20% yield from pyruvic acid.

SUBMITTER: Shirley HJ

PROVIDER: S-EPMC6471603 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of lamellarin alkaloids using orthoester-masked α-keto acids.

Shirley Harry J HJ Koyioni Maria M Muncan Filip F Donohoe Timothy J TJ

Chemical science 20190319 15

Pyruvic acid and other α-keto acids are frequently encountered as intermediates in metabolic pathways, yet their application in total synthesis has met with limited success. In this work, we present a bioinspired strategy that utilizes highly functionalized OBO (oxabicyclo[2.2.2]octyl) orthoester masked α-ketoacids as key intermediates for the construction of both type I and II lamellarin alkaloids. Lamellarin D was synthesized, via a key 1,4-dicarbonyl, in 7 steps and 22% yield from pyru ...[more]

PMID: 31057760

Similar Datasets

Protometabolic Reduction of NAD+ with α-Keto Acids.

Project description:Deciphering the origins of the chemistry that supports life has frequently centered on determining prebiotically plausible paths that produce the molecules found in biology. What has been less investigated is how the energy released from the breakdown of foodstuff is coupled to the persistence of the protocell. To gain better insight into how such coupled chemistry could have emerged prebiotically, we probed the reactivity of the ribodinucleotide NAD+ with small organic molecules that were previously identified as potential constituents of protometabolism. We find that NAD+ is readily reduced nonenzymatically by α-keto acids, such as pyruvate and oxaloacetate, during oxidative decarboxylation. In the presence of FAD and a terminal electron acceptor, the consumption of α-keto acids by NAD+ initiates a plausible prebiotic electron transport chain. The observed reactivity suggests that components of the RNA world were capable of initiating the chemistry needed to capture the energy released from catabolism to drive anabolism.

| S-EPMC8395669 | biostudies-literature

A convenient enantioselective decarboxylative aldol reaction to access chiral α-hydroxy esters using β-keto acids.

Project description:We show a convenient decarboxylative aldol process using a scandium catalyst and a PYBOX ligand to generate a series of highly functionalized chiral α-hydroxy esters. The protocol tolerates a broad range of β-keto acids with inactivated aromatic and aliphatic α-keto esters. The possible mechanism is rationalized.

| S-EPMC4077541 | biostudies-literature

Synthesis of alpha-keto-imides via oxidation of ynamides.

Project description:A de novo preparation of alpha-keto-imides via ynamide oxidation is described. With a number of alkyne oxidation conditions screened, a highly efficient RuO2-NaIO4 mediated oxidation and a DMDO oxidation have been identified to tolerate a wide range of ynamide types. In addition to accessing a wide variety of alpha-keto-imides, the RuO2-NaIO4 protocol provides a novel entry to the vicinal tricarbonyl motif via oxidation of push-pull ynamides, and imido acylsilanes from silyl-substituted ynamides. Chemoselective oxidation of ynamides containing olefins can be achieved by using DMDO, while the RuO2-NaIO4 protocol is not effective. These studies provide further support for the synthetic utility of ynamides.

| S-EPMC2720040 | biostudies-literature

Acid-Promoted Redox-Annulation toward 1,2-Disubstituted-5,6-dihydropyrrolo[2,1-α]isoquinolines: Synthesis of the Lamellarin Core.

Project description:An efficient synthesis of a variety of 1,2-disubstituted-5,6-dihydropyrrolo[2,1-α]isoquinoline derivatives via an acid-promoted cyclization reaction between 1,2,3,4-tetrahydroisoquinoline (THIQ) and substituted α,β-unsaturated aldehyde derivatives is reported. This cycloaddition allows access to structurally diverse multisubstituted dihydropyrrolo[2,1-α]isoquinolines in moderate to good yields, which was the core scaffold of marine natural alkaloid lamellarins.

| S-EPMC9608416 | biostudies-literature

Environmental Processing of Lipids Driven by Aqueous Photochemistry of α-Keto Acids.

Project description:Sunlight can initiate photochemical reactions of organic molecules though direct photolysis, photosensitization, and indirect processes, often leading to complex radical chemistry that can increase molecular complexity in the environment. α-Keto acids act as photoinitiators for organic species that are not themselves photoactive. Here, we demonstrate this capability through the reaction of two α-keto acids, pyruvic acid and 2-oxooctanoic acid, with a series of fatty acids and fatty alcohols. We show for five different cases that a cross-product between the photoinitiated α-keto acid and non-photoactive species is formed during photolysis in aqueous solution. Fatty acids and alcohols are relatively unreactive species, which suggests that α-keto acids are able to act as radical initiators for many atmospherically relevant molecules found in the sea surface microlayer and on atmospheric aerosol particles.

| S-EPMC5968514 | biostudies-literature

Asymmetric organocatalytic decarboxylative Mannich reaction using ?-keto acids: A new protocol for the synthesis of chiral ?-amino ketones.

Project description:The first decarboxylative Mannich reaction employing ?-keto acids, catalyzed by cinchonine-derived bifunctional thiourea catalyst has been described. The desired ?-amino ketones were obtained in excellent yields and with moderate to good enantioselectivities.

| S-EPMC3458749 | biostudies-literature

Total Synthesis of GE81112A: An Orthoester-Based Approach.

Project description:The GE81112 series, consisting of three naturally occurring tetrapeptides and synthetic derivatives, is evaluated as a potential lead structure for the development of a new antibacterial drug. Although the first total synthesis of GE81112A reported by our group provided sufficient amounts of material for an initial in depth biological profiling of the compound, improvements of the routes toward the key building blocks were needed for further upscaling and structure-activity relationship studies. The major challenges identified were poor stereoselectivity in the synthesis of the C-terminal β-hydroxy histidine intermediate and a concise access to all four isomers of the 3-hydroxy pipecolic acid. Herein, we report a second-generation synthesis of GE81112A, which is also applicable to access further representatives of this series. Based on Lajoie's ortho-ester-protected serine aldehydes as key building blocks, the described route provides both a satisfactory improvement in stereoselectivity of the β-hydroxy histidine intermediate synthesis and a stereoselective approach toward both orthogonally protected cis and trans-3-hydroxy pipecolic acid.

| S-EPMC10167690 | biostudies-literature

Enantioselective synthesis of α-amino ketones through palladium-catalyzed asymmetric arylation of α-keto imines.

Project description:Chiral α-amino ketones are common structural motifs in natural products and pharmaceuticals, as well as important synthons in organic synthesis. Thus, establishing efficient methods for preparing compounds with these privileged scaffolds is an important endeavor in synthetic chemistry. Herein we disclose a new catalytic asymmetric approach for the synthesis of chiral α-amino ketones through a chiral palladium-catalyzed arylation reaction of in situ generated challenging α-keto imines from previously unreported C-acyl N-sulfonyl-N,O-aminals, with arylboronic acids. The current reaction offers a straightforward approach to the asymmetric synthesis of acyclic α-amino ketones in a practical and highly stereocontrolled manner. Meanwhile, the multiple roles of the chiral Pd(ii) complex catalyst in the reaction were also reported.

| S-EPMC8966749 | biostudies-literature

Total Synthesis of Marine Alkaloids Motuporamines A and B via Ring Expansion of Cyclic β-Keto Esters.

Project description:An expedient total synthesis of the title marine sponge alkaloids has been developed. The salient features of the synthesis are as follows: (i) preparation of the required 13- and 14-membered cyclic lactams with n + 4 ring-expansion strategy of cyclic β-keto esters and (ii) functional group manipulation of the resulted keto ester lactams. This approach used easily accessible and inexpensive materials/reagents, thus providing a promising alternative to the existing preparations.

| S-EPMC7808158 | biostudies-literature

KI-catalyzed oxidative cyclization of α-keto acids and 2-hydrazinopyridines: efficient one-pot synthesis of 1,2,4-triazolo[4,3-a]pyridines.

Project description:A one-pot approach to substituted 1,2,4-triazolo[4,3-a]pyridines has been developed that is based on a KI-catalyzed oxidative cyclization of α-keto acids and 2-hydrazinopyridines. This transition-metal-free procedure was highly efficient and shows good economical and environmental advantages.

| S-EPMC9086216 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data